Kaposi sarcoma in human immunodeficiency virus infection, clinicopathologic correlation with coexisting patch and plaque stage features: A case report and review of literature

Abstract

BACKGROUND

Kaposi sarcoma (KS) is a human herpesvirus 8 (HHV-8)-associated vascular neoplasm frequently linked to advanced human immunodeficiency virus (HIV) infection and may clinically mimic several inflammatory, vascular, and melanocytic disorders. Early recognition is essential, as cutaneous lesions may represent the first indicator of undiagnosed immunosuppression. We report this case to emphasize the diagnostic value of overlapping histopathological features and clinicopathologic correlation in differentiating KS from its clinical mimickers.

CASE SUMMARY

A 45-year-old man presented with a 6-month history of progressively increasing violaceous papules and plaques on the abdomen and chest. Initial differential diagnoses included vascular, granulomatous, and melanocytic conditions. Skin biopsy revealed epidermal atrophy, elongation of rete ridges, dermal vascular proliferation, slit-like vascular spaces, spindle-cell proliferation, plasma-cell infiltrates, and extravasated erythrocytes, demonstrating coexisting histopathologic features of patch and plaque stage KS. Immunohistochemistry showed strong nuclear positivity for HHV-8 latent nuclear antigen-1, confirming the diagnosis. Subsequent testing identified previously undiagnosed HIV infection with a low CD4 count. Combination antiretroviral therapy was initiated, resulting in partial clinical regression of the lesions on follow-up.

CONCLUSION

Cutaneous KS may serve as an early indicator of occult HIV infection. Timely biopsy and HHV-8 confirmation enable early diagnosis and prompt initiation of antiretroviral therapy, thereby improving clinical outcomes.

Key Words: Kaposi sarcoma; Human herpesvirus 8; Latent nuclear antigen-1; Human immunodeficiency virus; Vascular tumors; Dermatopathology; Case report

Core Tip: Kaposi sarcoma may be the first clinical indicator of previously undiagnosed human immunodeficiency virus infection. This case demonstrates the coexisting histopathologic features of patch and plaque stages within a single biopsy specimen, highlighting key diagnostic features such as slit-like vascular spaces, spindle-cell proliferation, and confirmatory human herpesvirus 8 latent nuclear antigen-1 positivity. Recognition of these clinicopathological features is essential for differentiating Kaposi sarcoma from its mimickers and enables timely human immunodeficiency virus testing and early initiation of antiretroviral therapy, which may lead to lesion regression and improved clinical outcomes.

INTRODUCTION

Kaposi sarcoma (KS) is a low-grade angioproliferative neoplasm associated with infection by human herpesvirus 8 (HHV-8)[1]. It remains one of the most characteristic cutaneous manifestations of advanced human immunodeficiency virus (HIV) infection and serves as an important clinical sentinel sign that prompts investigation for underlying immunosuppression[1,2]. Clinically, KS may mimic several vascular, inflammatory, and pigmented lesions, which often broadens the initial differential diagnosis[3]. Epidemic HIV-associated KS typically presents with violaceous, erythematous, or hyperpigmented macules, papules, plaques, or nodules that may gradually enlarge, coalesce, or become raised over time[4]. The lesions are often multifocal and may involve the lower extremities, face, trunk, oral mucosa, genital region, and, in advanced disease, lymph nodes or visceral organs[5-7]. The variable morphology and distribution of KS lesions contribute to its clinical overlap with vascular, inflammatory, granulomatous, and melanocytic mimickers[8].

Histopathology remains central to diagnosis, revealing a spectrum of morphological changes that evolve from patch to plaque and ultimately to the nodular stage[9]. Immunohistochemical demonstration of HHV-8 latent nuclear antigen-1 (LANA-1) provides definitive confirmation[10]. Here, we present a case of KS in a previously undiagnosed HIV-positive adult man and outline the diagnostic challenges, key histopathological features, and clinical implications.

CASE PRESENTATION

Chief complaints

A 45-year-old man presented with progressively increasing violaceous cutaneous lesions over the abdomen and chest for 6 months.

History of present illness

The patient reported the gradual appearance of multiple asymptomatic violaceous papules that progressively enlarged and increased in number over 6 months, eventually evolving into plaques. He denied pain, pruritus, bleeding, mucosal involvement, or preceding dermatologic conditions. There were no associated constitutional symptoms, including fever, unintentional weight loss, night sweats, or fatigue. He also denied experience of recurrent infections or any history suggestive of opportunistic disease.

History of past illness

The patient had no known chronic medical conditions or prior history of dermatologic or immunologic disease.

Personal and family history

The patient denied smoking, alcohol consumption, or use of recreational drugs. He reported no history of high-risk sexual behavior, recent travel, or known exposure to infectious diseases. There was no history of immunosuppressive medication use or prior hospitalizations for severe or recurrent infections. Family history was negative for malignancies, vascular tumors, and autoimmune diseases.

Physical examination

Dermatologic examination revealed multiple well-defined violaceous papules and plaques, distributed across the anterior and lateral abdominal wall and mid-chest (Figure 1). No oral lesions, lymphadenopathy, or hepatosplenomegaly were detected. The remainder of the systemic examination was unremarkable. As there were no clinical features suggestive of systemic involvement, further imaging or staging investigations were not performed at the time of initial evaluation. Based on the clinical appearance of multiple violaceous papules and plaques with progressively increasing number and size, an initial differential diagnosis was formulated. Considerations included vascular proliferations such as bacillary angiomatosis and pyogenic granuloma, inflammatory and granulomatous conditions, and melanocytic lesions including melanoma. Although the vascular nature and multifocal distribution of the lesions raised clinical suspicion for a vascular neoplasm, a definitive diagnosis could not be established on clinical grounds alone due to the significant overlap with both benign and malignant entities. Therefore, a skin biopsy was performed for histopathologic evaluation.

Figure 1 Multiple well-defined violaceous papules and plaques present in the case.

Laboratory examinations

Serologic testing for HIV was positive. The CD4 lymphocyte count (341 cells/μL) was below the normal range (normal range: 500-1500 cells/μL), consistent with immunosuppression. The HIV viral load was > 10000000 copies/mL. Routine hematologic and biochemical investigations returned normal results otherwise.

Imaging examinations

Imaging evaluation was deemed unnecessary.

MULTIDISCIPLINARY EXPERT CONSULTATION

The case was reviewed collaboratively by dermatology, pathology, and oncology specialists. Histopathologic findings and clinical features were jointly evaluated, and a consensus was reached regarding the diagnosis and management plan.

Histopathological examination

Punch biopsy demonstrated hyperkeratosis, epidermal atrophy, elongation of rete ridges, and dermal proliferation of irregular vascular spaces (Figure 2A). The papillary dermis showed newly formed vascular channels lined by flattened endothelial cells entrapping pre-existing vessels, consistent with patch-stage disease (Figure 2B). The lower reticular dermis revealed slit-like vascular channels dissecting collagen bundles, accompanied by perivascular spindle-shaped cells, plasma cell-rich inflammatory infiltrates, and extravasated erythrocytes, consistent with features of the plaque stage occurring alongside patch-stage changes (Figure 2C). Immunohistochemistry demonstrated strong nuclear positivity for HHV-8 LANA-1, confirming the diagnosis of KS (Figure 2D).

Figure 2 Histopathological examination. A: Histopathologic findings. Hyperkeratosis, epidermal atrophy, elongation of rete ridges, and prominent dermal proliferation of irregular vascular spaces were present. Original magnification × 4, scale bar = 500 μm; B: Papillary dermis findings indicated patch stage. Newly formed vascular spaces lined by flattened endothelial cells, entrapping pre-existing blood vessels, were consistent with the patch stage. Hematoxylin and eosin original magnification 10 ×, scale bar = 200 μm; C: Lower reticular dermis findings indicated plaque stage. Slit-like vascular channels dissecting collagen bundles, with perivascular spindle-shaped cells, plasma cell-rich inflammatory infiltrates, and extravasated erythrocytes, were consistent with the plaque stage. Left image original magnification 20 ×, scale bar = 100 μm. Right image original magnification 40 ×, scale bar = 50 μm; D: Immunohistochemistry confirmed the diagnosis of Kaposi sarcoma. Human herpesvirus 8 latent nuclear antigen-1 staining showed strong nuclear positivity. Original magnification 20 ×, scale bar = 100 μm.

FINAL DIAGNOSIS

HIV-associated cutaneous KS.

TREATMENT

The patient was initiated on combination antiretroviral therapy (cART) consisting of tenofovir alafenamide, emtricitabine, and bictegravir. Following the multidisciplinary evaluation by dermatology and oncology teams, and considering the absence of clinical evidence of visceral involvement or extensive disease, a decision was made to manage the patient with antiretroviral therapy alone. Close clinical monitoring was recommended, with consideration of systemic or local KS-directed therapy if disease progression occurred.

OUTCOME AND FOLLOW-UP

The patient was reassessed at an early follow-up visit after initiation of cART. At that time, partial regression of the cutaneous lesions was observed, with reduction in erythema and flattening of plaques; in addition, no new lesions had developed. There was no clinical evidence of progression to nodular or visceral disease. The overall clinical course was consistent with an early response to immune reconstitution. Continued follow-up was planned to monitor for further regression or potential disease progression.

DISCUSSION

KS was first described in 1872 by Moritz Kaposi as an indolent, multifocal vascular tumor affecting elderly men of Mediterranean and Eastern European descent[11,12]. For decades, the disease was considered rare and of uncertain etiology, with diagnosis relying primarily on clinical appearance and routine histopathology[11,13,14]. The emergence of the HIV/acquired immunodeficiency syndrome epidemic in the late 20^th century dramatically altered the epidemiologic and clinical understanding of KS, revealing its strong association with immunosuppression[11,15]. Subsequent advances in pathology, molecular biology, and immunohistochemistry-particularly the discovery of HHV-8 in 1994-significantly improved diagnostic accuracy and refined disease classification[13,16]. The ability to detect HHV-8 using immunohistochemical markers such as LANA-1 has since established KS as a distinct viral-driven vascular neoplasm, allowing confident differentiation from histologic mimickers and facilitating earlier diagnosis[17].

KS should be considered in adults presenting with persistent violaceous plaques or nodules, especially when lesions are multifocal[9,18]. KS represents a unique vascular neoplasm whose development requires both infection with HHV-8 and an immunocompromised host environment, most commonly due to HIV infection[19]. Cutaneous involvement is frequently the earliest and most visible manifestation, often preceding systemic symptoms or formal HIV diagnosis[20-22]. As such, dermatologic recognition plays a significant role in uncovering underlying immunodeficiency. In the present case, the patient’s presentation largely conformed to the classical cutaneous description of epidemic HIV-associated KS. The lesions were multifocal, violaceous, and progressive, evolving from papules into plaques over 6 months, which is consistent with the expected clinical spectrum of KS. The distribution over the abdomen, lateral abdominal wall, and mid-chest also fell within the recognized truncal involvement for HIV-associated KS. However, there were no oral lesions, lymphadenopathy, hepatosplenomegaly, constitutional symptoms, or clinical evidence of visceral disease at presentation. Therefore, the case was not atypical in lesion morphology or anatomical distribution; rather, its main value for the literature lies in its demonstration of a strong clinicopathologic correlation and coexisting patch and plaque stage features reflecting the histopathologic continuum of disease in a patient whose cutaneous lesions led to the diagnosis of previously undetected HIV infection.

The clinical overlap between KS and other conditions, including vascular proliferations (bacillary angiomatosis), granulomatous processes (sarcoidosis, nodular granuloma annulare), melanocytic proliferations (Spitz nevus, blue nevus), and infiltrative conditions (leukemia cutis, pigmented dermatofibroma), makes histopathologic confirmation essential[18,23-25]. Clinically, these entities may present as violaceous or pigmented papules and nodules, particularly in the early stages of KS, leading to diagnostic uncertainty[23,26]. In HIV-positive individuals, bacillary angiomatosis is a particularly important mimic, as it can present with similar vascular lesions but requires entirely different management[26,27]. In this case, histopathologic evaluation revealed slit-like vascular spaces, spindle-cell proliferation, plasma cell-rich inflammatory infiltrates, and extravasated erythrocytes, all of which are characteristic of KS. In contrast, bacillary angiomatosis typically demonstrates lobular capillary proliferation with prominent neutrophilic inflammation and the presence of bacilli, which were not observed in this specimen. Furthermore, immunohistochemical staining showed strong nuclear positivity for HHV-8 LANA-1, which is diagnostic of KS and effectively excludes other vascular proliferations that lack HHV-8 infection. Therefore, tissue diagnosis remains indispensable.

This case demonstrates the classical histopathologic continuum of KS, with coexistence of features corresponding to both patch and plaque stages within a single biopsy specimen, including: (1) Early proliferation of jagged, irregular vascular spaces; (2) Progressive formation of slit-like channels dissecting collagen; (3) Spindle-cell expansion with inflammatory infiltrates; (4) Erythrocyte extravasation with hemosiderin deposition; and (5) Eventual development of nodular architecture. These morphologic changes reflect disease progression from patch to plaque stages and show the dynamic overlapping nature of KS histopathology, rather than a strictly time-dependent sequential progression. The presence of both early vascular proliferation and more advanced spindle-cell and slit-like vascular channel formation highlights the spectrum of morphologic changes that may be encountered simultaneously in clinical practice. The presence of plasma cell-rich inflammatory infiltrates and extravasated red blood cells further supports the diagnosis and helps distinguish KS from other vascular tumors[28].

Confirmatory HHV-8 (LANA-1) staining is considered the most reliable method for establishing diagnosis of KS[29,30]. Nuclear positivity for LANA-1 within endothelial and spindle cells establishes HHV-8 infection and definitively differentiates KS from its histologic mimickers[29,30]. Immunohistochemistry is particularly valuable in early lesions, where vascular proliferation may be subtle and architectural features are less well developed.

The cutaneous presentation prompted HIV testing, which revealed a previously undiagnosed infection. Historically, in the pre-antiretroviral therapy era, KS was among the most common acquired immunodeficiency syndrome-defining illnesses and frequently represented the initial clinical manifestation leading to HIV diagnosis, particularly among high-risk populations[31]. The introduction of cART has led to a substantial decline in the incidence of KS, primarily due to earlier detection of HIV infection and improved immune preservation[32,33]. Despite this progress, KS continues to present as the first indicator of previously undiagnosed HIV infection in a subset of patients, especially in cases of delayed diagnosis or limited healthcare access[32,34]. This highlights the ongoing importance of recognizing KS as a potential sentinel condition for underlying immunosuppression, even in the modern cART era. Despite declining incidence in regions with early HIV diagnosis and treatment, KS remains an important diagnostic consideration, particularly in patients who present late or without known risk factors[35].

KS often regresses with immune restoration following cART, emphasizing the importance of early diagnosis[36,37]. Initiation of antiretroviral therapy alone may lead to partial or complete regression of cutaneous lesions through immune reconstitution, reducing the need for systemic chemotherapy in selected cases[37-39]. Therefore, early recognition not only facilitates appropriate oncologic evaluation but also has a significant impact on prognosis[11].

This case reinforces the value of dermatologic findings as early clinical markers of systemic disease. Awareness of the clinical and histopathologic spectrum of KS enables timely diagnosis, appropriate HIV screening, and early initiation of appropriate therapy. Importantly, this case is not presented as a rare demographic or clinically atypical manifestation of KS but rather as an educationally significant example that reinforces key diagnostic principles. Its value lies in the clear demonstration of clinicopathologic correlation, particularly the coexistence of patch and plaque stage histopathologic features within a single biopsy specimen, reflecting the dynamic progression of KS. Furthermore, the absence of preceding constitutional symptoms or identifiable risk factors emphasizes the role of KS as a potential initial and sometimes sole indicator of underlying HIV infection. Maintaining a high index of suspicion and pursuing timely histopathologic evaluation in patients presenting with compatible cutaneous findings remains crucial.

CONCLUSION

The characteristic clinical and histopathologic features of KS can be characterized as an early indicator of underlying immunosuppression. While this case of KS in HIV is not rare in its presentation, its significance lies in demonstrating the clear clinicopathologic correlation and coexisting histopathologic features reflecting different stages of disease evolution within a single case. The absence of preceding systemic symptoms in this patient further highlights the potential for KS to serve as the first manifestation of previously undiagnosed HIV infection. Early biopsy, confirmatory HHV-8 (LANA-1) immunostaining, and prompt initiation of antiretroviral therapy remain essential for accurate diagnosis and optimal patient outcomes.